A diagnosis of Lyme disease was made in a 71-year-old patient with fever, chills, and generalized weakness, but concurrent babesiosis was initially missed. A technician in the hematology laboratory noticed intraerythrocytic organisms initially thought to be Plasmodium, but close inspection of the blood smear and review of the patient's history pointed to infection with Babesia.

Introduction

Babesia species are intraerythrocytic protozoans that cause a spectrum of illness in humans, ranging from asymptomatic infection to cardiac, renal, pulmonary, and CNS complications to death.[1] Most manifestations are, however, subclinical.[2] Patients with babesiosis present with fever, chills, malaise, weakness, anorexia, hemolysis, and hemoglobinuria. Babesiais a zoonotic organism transmitted to humans by the arthropod vector Ixodes dammini. Other agents of tick-borne illness include Borrelia burgdorferi, Ehrlichia equi, and Ehrlichia chaffeensis. Cases of cotransmission have been described.[3-7]

Case Report

History

A previously healthy 71-year-old man was admitted to the hospital with fevers, chills, and generalized weakness. He had been in his usual state of health until 1 week before admission, at which time fatigue, anorexia, fevers, and chills developed. He visited his internist, who initiated an outpatient workup; however, the patient became more lethargic, and his family brought him to the emergency department.

The patient recalled having eaten shellfish approximately 8 to 10 days earlier without subsequent nausea, vomiting, diarrhea, or abdominal pain. He admitted to drinking 2 to 3 glasses of red wine daily. His travel history included the summer spent on the eastern end of Long Island, NY; he returned 2 weeks before admission. He had spent time gardening but was unaware of any tick bites. There was no history of recent blood transfusion, and he was a nonsmoker.

Physical and Laboratory Examination

The oral temperature was 37.3°C (99.1°F); pulse, 95 beats per minute and regular; respirations, 18 breaths per minute; and blood pressure, 103/57 mm Hg. The patient appeared noticeably jaundiced and had scleral icterus. No rashes were visible. Lungs, heart, abdomen, and extremities were normal. No hepatosplenomegaly was appreciated. Results of a guaiac test for occult blood in stool were negative. Blood chemistries and hematologic values are presented in Tables 1 and 2, respectively. Results of an ECG and chest radiographs were normal.

These initial findings were suggestive of alcoholic hepatitis, and supportive treatment was initiated.

Hospital Course

The abdominal sonogram revealed a normal liver, contracted callbladder, normal pancreas, normal kidneys, and splenomegaly (13.2 cm). Results of hepatitis serology were positive only for hepatitis A IgG. On hospital day 3, a peripheral blood smear showed greater than 50% intraerythrocytic inclusion bodies. The thin smear was consistent with babesiosis, as shown in the Figure.

Figure1. Intraerythrocytic trophozoites of Babesia microti.

Therapy was started with oral quinine and intravenous clindamycin, but the patient continued to do poorly, with persistently elevated levels on liver function tests and depressed platelet counts. Blood was sent for testing for both Lyme disease and Ehrlichia infection, and doxycycline was empirically added to the patient's regimen. On hospital day 5, the patient underwent exchange transfusion.

Lyme titers returned positive (IgG/IgM antibodies, 3.31 test units [TU]; [1.0 TU or greater is considered positive]) by traditional enzyme-linked immunosorbent assay and were confirmed by Western blot, while results of both indirect fluorescent antibody and polymerase chain reaction (PCR) tests for Ehrlichia were negative. The patient's parasitemia improved to less than 1% after exchange transfusion and was 0% on discharge on hospital day 14, at which time he had completed a 7-day course of treatment with quinine and clindamycin.

This patient had many symptoms and signs of babesiosis, yet the admitting physician missed the diagnosis. The diagnosis of babesiosis was not considered until an astute technician in the hematology laboratory noticed intraerythrocytic organisms, thought initially to be malaria parasites. Close inspection of the smear in conjunction with the patient's clinical history suggested infection with Babesia.

Pathogen and Pathogenesis

Human babesiosis is a zoonosis caused by protozoa of the order Piroplasmida, the family Babesiidae, and the genus Babesia. There are more than 99 species of Babesia in the world that infect various hosts and are transmitted by multiple vectors. In 1957, the first reported case of babesiosis in humans was described in a splenectomized young Yugoslavian man in whom an acute febrile illness developed with hemoglobinuria, anemia, and ultimately death.[8] In humans, only a small percentage of species have been shown to cause illness. In Europe, the infectious agent is of bovine species (Babesia divergens and Babesia bovis), and in the United States, the patients are infected with the rodent species Babesia microti. In the western United States, a newly recognized species, WA-1, has been documented to cause clinical disease.[9,10] The parasites vary in length from 1 to 5 µm and may appear pear-shaped, oval, or round.

Transmission of B microti usually occurs via the tick vector I dammini. There are 3 stages of development (larva, nymph, and adult); each requires a blood meal in order to progress to the next stage. Both the larvae and nymphs are capable of infecting humans. The adult tick, which feeds primarily on the white-tailed deer, is also capable of transmitting infection to humans.[2]

On transmission from the salivary glands of the tick, merozoites will parasitize the erythrocytes, forming trophozoites. By way of synchronous, asexual budding or binary fission, each trophozoite then gives rise to 2 or 4 merozoites; the tetrad is classically referred to as the "Maltese cross."[11] There appears not to be an exoerythrocytic stage.

It has been suggested that erythrocytic invasion occurs via a complement-mediated pathway, resulting in red cell membrane abnormality with decreased deformability.[2,12,13] The change in lipid composition in the red blood cell membrane makes parasitized cells more cytoadherent to endothelial cells.[14] The ensuing hemolytic anemia is hypothesized to result from capillary sequestration.[13] Since the pathway of schizogony is asynchronous, the anemia is generally not a massive hemolysis, such as occurs in Plasmodium infection; in some cases, the anemia may be related to disseminated intravascular coagulation.[12]

Epidemiology

In the United States, the most common pathogen of babesiosis is B microti. The infection is endemic in coastal regions of the northeastern United States, such as Nantucket, Martha's Vineyard, and Cape Cod, Mass; Block Island, RI; and Shelter Island and eastern Long Island, NY.[2] Other areas include Connecticut, Wisconsin, and California.[15-17] Most cases occur during the spring and early summer. In an epidemiologic study of babesiosis in New York in 1992, 90% of 123 cases occurred during the months of June through August.[18]

Lyme disease is endemic in the same geographic locations, since the same vector transmits both diseases. As a result, much of the epidemiologic data we have for Lyme disease may potentially be applied to babesiosis. Both reservoir and vector (the white-tailed deer and the Ixodes tick, respectively) populate these locations. Patients infected with the WA-1 strain of Babesia have been from areas of Washington and northern California; however, neither the vector nor the host has yet been described.[9,10] Patients may also become infected by receiving blood products (erythrocytes, platelets) from infected donors with asymptomatic parasitemia.[19] In addition, cases of vertically transmitted Babesia have been described. In 2 cases, a history of tick bites was ascertained without ensuing smear evidence of parasitemia in the mothers, but there was serologic evidence of acute infection. Parasitemia developed in both infants.[20,21]

Clinical Features

Symptoms usually begin 1 to 4 weeks after a tick bite or 6 to 9 weeks
post-transfusion with infected blood products. The severity of signs and symptoms varies among infecting species. In Europe, both B divergens and B bovis cause fatal illness in asplenic patients. In the United States, B microti causes less severe disease in patients with an intact spleen, and the disease rarely results in death. The signs and symptoms are gradual in onset and include constitutional symptoms, anorexia, abdominal pain, and dark urine. The fever of babesiosis is not typically cyclical, as it is with malaria. Patients may or may not recall any tick bites, but most often, there is a history of outdoor activity or travel to an area where the disease is endemic.

Physical examination findings include fever, jaundice, hepatomegaly, and splenomegaly. Table 3 lists common manifesting symptoms and signs of babesiosis. Laboratory data suggest hemolytic anemia with decreased hematocrit, elevated total and direct bilirubin levels, elevated lactate dehydrogenase level, reticulocytosis, and elevated hepatic transaminase levels. Urinalysis reveals hemoglobinuria without red blood cells. The intensity of parasitemia can vary; the parasite may be undetectable, or its concentration can be greater than 85%.[22]

Prognostic Features

Risk factors for more severe outcome include male sex, alkaline phosphatase levels greater than 125 U/L, and white blood cell counts greater than 5 3 10[9]/L.[23] A history of splenec-tomy or functional asplenia and immunodeficiency (lymphoma or AIDS) are 2 other important risk factors that portend the development of clinically apparent disease or protracted illness. However, most patients with symptomatic babesiosis with a history of asplenia were infected with B divergens or the WA-1 strain. Patients infected with B microti are usually asymptomatic.

Diagnosis

The diagnosis of babesiosis may be based on Wright- or Giemsa-tained peripheral blood smears, immunofluorescent antibody tests, and/or PCR assay. Peripheral smear may reveal parasitized erythrocytes with organisms at various stages of development, consistent with the asynchronous replication of progeny. In cases of very low parasitemia, the smear may not demonstrate the intraerythrocytic parasites or the characteristic Maltese cross tetrads. Unlike in malaria, there are no schizonts or gametocytes. To avoid overlooking the correct diagnosis in the setting of a negative peripheral blood smear, suspicion should remain high and serologic studies and PCR should be pursued, especially if there is a history of travel to locations where the disease is endemic or of splenectomy with acute febrile illness and anemia. Serologically, a titer greater than 1:64 indicates a positive result or seropositivity, and a titer greater than 1:256 suggests an acute infection.[22] Quantification of the titer has not been shown to correlate with the severity of illness. PCR is a more sensitive test and may also be used to monitor progression or resolution of infection. In addition, PCR testing may detect persistent infection in patients with prolonged symptoms.[24,25]

Treatment

Treatment should be initiated early in symptomatic patients to avoid massive hemolysis with ensuing renal failure. Cases of subclinical infection need not be treated. Recommended treatment is with oral quinine, 650 mg every 6 to 8 hours, and with intravenous clindamycin, 1200 to 2400 mg every 6 to 8 hours, for 7 days. Side effects of quinine include hemolytic anemia (precaution should be taken in patients with glucose-6-phosphate dehydrogenase deficiency), thrombocytopenia, tinnitus, vertigo, hearing loss, lupus rash, gastric distress, and QT prolongation. This medication should not be administered to pregnant patients. In those who are unable to tolerate quinine, a combination of clindamycin with azithromycin and doxycycline has been used.[26] The combination of atovaquone and azithromycin has been shown to be an effective and better-tolerated alternative regimen.[27] In patients who are refractory to pharmacologic management, exchange transfusion with red blood cells has been shown to expedite recovery, probably secondary to diminishing the parasite load.[28]

Patients may remain parasitized despite adequate therapy with resolution of symptoms, with positive PCR test results raising the question of a possible exoerythrocytic stage.[25] Some patients may even require maintenance therapy to prevent recrudescence.

Cotransmission

It is important to keep in mind other tick-borne organisms that may be cotransmitted with Babesia, such as B burgdorferi (the agent of Lyme disease) and Ehrlichia species (the agent of human granulocytic ehrlichiosis).[3,5-7] Similar geographic and seasonal distribution as well as common vectors are likely responsible for this occurrence. An epidemiologic study of 136 cases of babesiosis showed that as many as 23% had concurrent Lyme disease based on clinical and serologic data.[14] In 2 separate studies, 10% of patients with Lyme disease were found to be coinfected with B microti on the basis of serologic and PCR test results.[6,7] In a study of 55 patients with confirmed Lyme infection, 2 patients had positive antibodies to Ehrlichia species.[6] Another study demonstrated cotransmission of both B microti and B burgdorferi in hamsters by disease-infected nymph forms of I dammini.[5] Taken together, these studies emphasize the need to consider coinfection with other tick-borne illnesses when the diagnosis of 1 is made.

Coinfection is thought to cause more severe illness than does disease with 1 organism alone.[4] The pathophysiologic explanation is yet to be described, although speculation suggests an immunosuppressive role of Babesia as a possibility.[6]

A total of 1,367 Ixodes ricinus ticks collected from 5 districts of the Lublin region (eastern Poland) were examined for the presence of Babesia microti DNA by PCR and nested-PCR. As many as 74 ticks (5.4 %) were found to be infected with Babesia microti. The infection rate varied significantly with stage/sex of ticks chi (2) =16.48543, df=2, p < 0.000264). The infection rates in females and males amounted to 6.4 % and 8.8 % respectively and were significantly higher (p=0.006 and p=0.0001 respectively) compared to minimum infection rate in nymphs that was equal to 2.8 %. The prevalence of infection showed also significant variability depending on geographic location within the Lublin region (chi(2) =18.62812, df=4, p < 0.000932). The highest rates of infection with Babesia microti were noted in ticks collected from the areas of Pulawy district situated in the northern part of region and the suburban Lublin district situated in the central part of the region (8.0 % and 7.3 % respectively). Mediocre infection rates (respectively 3.4 % and 3.3 %) were found in ticks from the Parczew and Wlodawa districts situated in eastern part of the region and covered with humid lakeland forests. The lowest infection rate (0.5 %) was noted in ticks from the Zamosc district situated in southern part of the region.

In conclusion, the infection rate of Ixodes ricinus ticks with Babesia microti found in this study is higher compared to the majority of data reported by Polish and other European authors, and indicates a potential risk of human infection during occupational or recreational exposure to tick bite.

Persistent Detection of Babesia EU1 and Babesia microti in Ixodes ricinus in The Netherlands During a 5-Year Surveillance: 2003-2007.
Wielinga PR, Fonville M, Sprong H, Gaasenbeek C, Borgsteede F, Giessen JW.
National Institute for Public Health and the Environment (RIVM), Laboratory for Zoonoses and Environmental Microbiology, Bilthoven, The Netherlands.

We report the finding of Babesia EU1 and Babesia microti in Ixodes ricinus ticks in the Netherlands. During 5 years of surveillance between 2003 and 2007, 1488 ticks were collected in a dune forest area near the North Sea and were screened for Babesia infections. In 17 ticks, DNA of the protozoan parasite genus Babesia was detected using a Babesia-specific 18S rRNA polymerase chain reaction. Further, reverse line blot analysis and DNA sequence analysis showed that 13 of these ticks carried Babesia EU1, two ticks carried B. microti, and one tick carried B. divergens. This study shows that the human pathogenic species Babesia EU1 and B. microti can complete their life cycle in the Netherlands.

Received 8 July 2003/ Returned for modification 8 July 2003/ Accepted 3 October 2003

We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.

Babesia are malaria-like parasites of man and animals. Babesia microti hasbeen identified as a newly emerging infection along the Eastern seaboardfrom Cape Cod to New Jersey. The major vector associated with its spreadis the deer tick (Ixodes scapularis) ï¿½ the same tick associated with Lyme disease. Investigators in Japan studied the effect of various heparins on this parasite and found that, depending on the concen-tration of heparin, there may be complete clearance of intracellular parasites! The findings suggest that the heparin coats the surface of the parasite and inhibits its invasion of the red cells. Bork, S. et al. 2004. Growth-inhibitory effect of heparin on Babesia parasites. AntimicrobialAgents and Chemotherapy 48: 236-241.

To determine characteristics of natural transmission of Babesia sp. EU1 and B. divergens by adult Ixodes ricinus ticks, we examined tick salivary gland contents. We found that I. ricinus is a competent vector for EU1 and that their sporozoites directly invade erythrocytes. We conclude that EU1 is naturally transmitted by I. ricinus.

(...)
Conclusions
Our study shows that I. ricinus ticks are competent vectors for Babesia sp. EU1. Not only can these ticks carry Babesia sp. EU1 DNA, but more importantly, they enable these parasites to complete their life cycle up to the production of infectious sporozoites. ***Direct invasion of erythrocytes by Babesia sp. EU1 undoubtedly classifies this species in the genus Babesia, a feature generally not proven for most Babesia spp.

The proportions of Babesia sp. EU1-infective ticks found in our study (3/223 from cattle farm and 2/31 from wild fauna reserve, not statistically different) are comparable to published prevalence of infected ticks (1%-2%) collected either from animals or vegetation (6-8,14,15). Whatever the biotope, Babesia sp. EU1 is always present, threatening also in anthropized zones (farming areas). ****Millions of parasites inside salivary glands were observed and could be injected to the vertebrate host, from the early stage of the tick feeding**** (11.7 mg) until repletion (277 mg), which represents a massive infection. These 2 epidemiologic features, combined with the increasing number of immunocompromised persons, should lead to more awareness of the risk related to this zoonotic pathogen.

In the past decade, cases of babesiosis in humans have been reported with increasing frequency, especially in the northeastern United States. Babesia microti (in the United States) and bovine strains (in Europe) cause most infections in humans. Most cases are tick-borne, although cases of transfusion-associated and transplacental/perinatal transmission have also been reported. Factors associated with more severe disease include advanced age, previous splenectomy and immunodeficient states. Symptoms include high fever, chills, diaphoresis, weakness, anorexia and headache. Later in the course of the illness, the patient may develop jaundice. Congestive heart failure, renal failure and acute respiratory distress syndrome are the most common complications. Therapy using the combination of quinine sulfate and clindamycin was the most commonly used treatment; however, atovaquone suspension plus azithromycin was recently reported an equally effective and less toxic therapy. Exchange transfusion, together with antibabesial chemotherapy, may be necessary in critically ill patients. (Am Fam Physician 2001;63:1969-74,1976.)

A patient information handout on babesiosis, written by the author of this article, is provided on page 1976.

A PDF version of this document is available. Download PDF now (6 pages / 446 KB). More information on using PDF files.

Babesiosis is a worldwide tick-borne hemolytic disease that is caused by intraerythrocytic protozoan parasites of the genus Babesia. The book of Exodus refers to a plague of "murrain" (hemoglobinuria) among cattle and other domestic animals. Possibly, this biblical reference was the first historical mention of babesial infection.1-3 Intraerythrocytic piroplasms consistent with Babesia were first described by Babès in 1888 in his evaluation of the cause of febrile hemoglobinuria in cattle in Romania.1-3

In the past decade, cases of babesiosis in humans have been reported with increasing frequency, especially along the northeastern coast of the United States. The aim of this article is to summarize the current knowledge of this infection and provide guidance to clinicians.

Pathogenesis

Most cases of babesiosis are tick-borne, but cases of transfusion-associated and transplacental/perinatal transmission have also been reported.

Of the more than 100 species of Babesia, Babesia microti (in the United States) and Babesia divergens and Babesia bovis (in Europe) cause most infections in humans. B. microti also infects various small mammals and primates, while B. divergens has been found to infect rats and gerbils as well as its main bovine host. Recently, a previously unknown species of Babesia (WA-1) was isolated from an immunocompetent man in Washington state who had clinical babesiosis.4,5 Researchers also described another probable new babesial species (MO1) associated with the first reported case of babesiosis acquired in the state of Missouri. MO1 is probably distinct from B. divergens but the two share morphologic, antigenic and genetic characteristics.6

Ixodid (or hard-bodied) ticks, in particular Ixodes dammini (Ixodes scapularis) and Ixodes ricinus, are the vectors of the parasite. Ticks ingest Babesia while feeding off the host, and the parasite multiplies within the tick's gut wall. The parasites then spread to the tick's salivary glands. Inoculation into a vertebrate host occurs by a tick larva, nymph or adult.2,3 Infection in humans usually occurs from late spring to early fall.

After an infectious tick bite, the parasites invade red blood cells and a trophozoite differentiates, replicating asexually by budding with the formation of two to four merozoites. A second type of undifferentiated trophozoite is also formed that does not replicate but enlarges and differentiates into gametocyte-like forms similar to that seen in Plasmodium species. Merozoites eventually disrupt infected erythrocytes and reinvade other red blood cells.1-3

Epidemiology

Babesiosis has rarely been reported outside the United States. Sporadic cases have been reported from a number of countries including France, the former Yugoslavia, United Kingdom, Ireland, the former Soviet Union and Mexico. In the United States, infections have been reported from many states but the most endemic areas are the islands off the coast of Massachusetts (including Nantucket and Martha's Vineyard) and New York (including eastern and south central Long Island, Shelter Island and Fire Island) and in Connecticut.1-3,7,8 In these areas, asymptomatic human infection seems to be common.

Between 1968 and 1993, more than 450 Babesia infections were confirmed in the United States by blood smears or serologic testing, but the prevalence of babesiosis is difficult to estimate because of lack of surveillance, and because infections are often asymptomatic. A recent study9 evaluated the seroprevalence and seroconversion for tick-borne diseases in a high-risk population in the northeast United States. In this one-year seroconversion study of patients in New York state who were at high risk for tick-borne diseases, antibodies to B. microti were seen in seven of 671 participants (1 percent), including one asymptomatic seroconversion during the year of observation.9

Transfusion-associated babesiosis has also been described.10 The risk factors for the donors have included exposure to endemic areas and being a recipient of blood transfusions. Patients receiving erythrocyte transfusions are at highest risk, while infection after transfusion of plasma has not been reported. In a survey of 779 blood donors in Cape Cod, Mass., seropositivity ranged from 3.3 to 4.9 percent, which was comparable with that in Boston, a nonendemic area.11

Overall, the risk of acquiring babesiosis from a blood transfusion is very low. In Connecticut, the risk of acquiring babesiosis from a transfused unit of packed red blood cells was estimated at about 0.17 percent (95 percent CI, 0.004 to 0.9 percent) and was even lower from a transfused unit of platelets (95 percent CI, 0.0 to 0.8 percent).12 Finally, transplacental/perinatal transmission has been reported.2,3

Clinical Features

Babesiosis in the United States has varied substantially from that described in Europe. To date, most of the patients described in Europe have been asplenic, have presented with acute febrile hemolytic disease and their clinical courses have almost always been fatal.2,3

In the United States, the clinical spectrum of the infection ranges from asymptomatic to rapidly progressive and fatal. Although babesiosis can affect persons of all ages, most patients present in their 40s or 50s. After a recognized tick bite, the incubation period of babesiosis varies from five to 33 days.1,3,7 However, most patients do not recall recent tick exposure. After an infected blood transfusion, the incubation period can be up to nine weeks.2,3,7,8

Both humoral and cell-mediated immune mechanisms influence the outcome of the infection. Factors associated with more severe disease include advanced age, previous splenectomy and immunodeficiency states including acquired immunodeficiency syndrome.7,13,14

Symptoms include high fever (up to 40°C [104°F]), chills, diaphoresis, weakness, fatigue, anorexia and headache (Table 1). Later in the course of the illness, the patient may develop jaundice and dark urine. Physical examination may reveal hepatomegaly and splenomegaly or evidence of shock. Rash is an uncommon symptom in babesiosis.1,2,3,7 Signs of central nervous system involvement include headache, photophobia, neck and back stiffness, altered sensorium and emotional lability.3,7,15

Congestive heart failure, disseminated intravascular coagulation and acute respiratory distress syndrome (that can occur even a few days after the onset of effective antimicrobial treatment) are the most common complications of human babesiosis (Table 2). Renal failure and myocardial infarction also have been associated with severe babesiosis. Researchers reviewed the clinical data and prognostic factors among 139 hospitalized cases in New York state between 1982 and 1993.16 Nine patients (6.5 percent) died, one fourth of the patients were admitted to the intensive care unit and one fourth of the patients required hospitalization for more than 14 days. The most common symptoms were fatigue/malaise/weakness (91 percent), fever (91 percent), shaking chills (77 percent) and diaphoresis (69 percent). Fifty-two percent of patients had a history of chronic disease. On average, a 12- to 14-day delay was noted between onset of symptoms and initiation of appropriate antibiotic treatment. Alkaline phosphatase levels greater than 125 U per L, white blood cell counts greater than 5 X 109 per L, history of cardiac abnormality, history of splenectomy, presence of heart murmur and parasitemia values of 4 percent or higher were associated with disease severity.16

Diagnosis

Mild to severe hemolytic anemia and a normal to slightly depressed leukocyte count are common nonspecific findings in babesiosis. Usually, the diagnosis is based on typical morphologic picture on the blood smear in conjunction with epidemiologic information. A Wright- or Giemsa-stained peripheral blood smear is most commonly used to demonstrate the presence of intraerythrocytic parasites (Figure 1). Rarely, tetrads of merozoites are visible.

The organisms are intraerythrocytic ring forms closely resembling Plasmodium, the organism causing malaria. Three distinguishing features differentiate the two organisms. Babesial organisms usually form tetrads ("Maltese cross"), do not have hemozoin pigments within the affected red blood cells and have extracellular merozoites.17,18

Serologic evaluation with the indirect immunofluorescent antibody test with use of B. microti antigen is available in a few laboratories. The cutoff titer for determination of a positive result varies with the particular laboratory protocol used, but in most laboratories, titers of more than 1:64 are considered consistent with B. microti infection. Tenfold to 20-fold higher titers can be observed in the acute setting, with a gradual decline over weeks to months. The correlation between the level of the titer and the severity of symptoms is poor.1-3

Detection of B. microti by polymerase chain reaction (PCR) was first described in 1992.19 A more recent study,20 in which PCR was used prospectively for diagnosing suspected cases in the northeastern United States has shown that PCR is more sensitive and equally specific for the diagnosis of acute cases, in comparison with direct smear examination and hamster inoculation. PCR-based methods may also be indicated for monitoring of the infection.20

Treatment

Babesiosis may continue for more than two months after treatment and when left untreated, silent babesial infection may persist for months or even years. Researchers21 compared the duration of parasitemia in persons who had received specific antibabesial therapy with that in silently infected persons who had not been treated. Babesial DNA persisted for 16 days in 22 acutely ill subjects who received clindamycin and quinine therapy (P = 0.03). Among the subjects who did not receive specific therapy, symptoms of babesiosis persisted up to 114 days.21

Treatment with the combination of quinine (Quinamm; 650 mg of salt orally, three times daily) and clindamycin (Cleocin; 600 mg orally, three times daily, or 1.2 g parenterally, twice daily) for seven to 10 days is the most commonly used treatment. The pediatric dosage is 20 to 40 mg per kg per day for quinine and 25 mg per kg per day for clindamycin. The fortuitous discovery of this regimen for babesiosis in humans was made during the management of a patient with presumed transfusion-acquired malarial infection. The patient was initially treated with chloroquine (Aralen Injection); however, because of lack of response, treatment was changed to quinine and clindamycin.2,3,22,23

Several other drugs have been evaluated, including tetracycline, primaquine, sulfadiazine (Microsulfon) and pyrimethamine (Fansidar). Results have varied. Pentamidine (Pentam) has proved to be moderately effective in diminishing symptoms and decreasing parasitemia.

Atovaquone suspension (Mepron; 750 mg twice daily) plus azithromycin (Zithromax; 500 to 1,000 mg per day) is a very effective treatment. This treatment was found to be effective for the prevention and treatment of babesiosis in hamsters. Clindamycin plus quinine was also effective but less so than atovaquone. When treatment was not started until parasitemia became established, atovaquone in dosages of 300, 150 and 80 mg per kg per day was effective in the recovery of all animals compared with 50 percent of those receiving 10 mg per kg per day and 10 percent of untreated control subjects.24 Of note is that, in the same model, when atovaquone was used as monotherapy, the disease recurred. Organisms obtained from these animals, when inoculated into uninfected animals, proved to be unresponsive to atovaquone therapy, suggesting the emergence of drug resistance. Resistant organisms did not emerge in hamsters treated with the combination of atovaquone and azithromycin.25

In humans, a prospective, randomized study26 comparing the efficacy of clindamycin and quinine with that of atovaquone and azithromycin has been conducted. This study included 58 patients with non­life-threatening babesiosis. Forty received atovaquone and azithromycin and 18 received clindamycin and quinine. The resolution of symptoms and parasitemia were similar between the two groups and both treatments were effective for all patients. However, 72 percent of the patients who received quinine and clindamycin suffered side effects from the antibiotics, compared with 15 percent of patients in the atovaquone and azithromycin group.26

Exchange transfusion, together with antibabesial chemotherapy, may be necessary in critically ill patients. This treatment is usually reserved for patients who are extremely ill--with blood parasitemia of more than 10 percent, massive hemolysis and asplenia.17

Prevention

Prevention of babesiosis involves avoiding endemic regions during the peak transmission months of May through September. This recommendation may be especially relevant for asplenic or immunocompromised persons in whom babesiosis can be a devastating illness.1,2 Using insect repellant is advised during outdoor activities, especially in wooded or grassy areas. One of the most effective tick repellents is N,N-diethyl-m-toluamide (DEET). It is commercially available in concentrations up to 100 percent. However, serious toxic and allergic reactions have been reported in persons who have used it frequently or in high concentrations. In young children, toxic encephalopathy has occurred.2,3 Products with 10 to 35 percent DEET will provide adequate protection under most conditions.

Early removal of ticks is important; the tick must remain attached for at least 24 hours before the transmission of B. microti occurs. Therefore, daily self-examination is recommended for persons who engage in outdoor activities in endemic areas. Pets also must be examined for ticks because they may carry ticks into the home.

Co-infection with Other Species of Tick-Transmitted Diseases

Co-infection with Borrelia burgdorferi and B. microti may be relatively common in endemic areas of the northeastern and upper midwestern United States. Approximately 10 percent of patients with Lyme disease in southern New England are co-infected with babesiosis in sites where both diseases are zoonotic. The number of symptoms and duration of illness in patients with concurrent Lyme disease and babesiosis are greater than in patients with either infection alone.27,28

Co-infection with Ehrlichia species may also be seen. Three species of Ehrlichia have been described that infect humans, Ehrlichia chaffeensis, Ehrlichia phagocytophila and Ehrlichia ewingii. Typically, patients have a nonspecific febrile illness. Rash is uncommon with human granulocytic ehrlichiosis but common with human monocytic ehrlichiosis. Laboratory findings often include leukopenia, thrombocytopenia and increases in serum hepatic enzyme activities. In areas endemic for Lyme disease and ehrlichiosis, it may be advisable to add doxycycline (Vibramycin), 100 mg twice a day by mouth, in the management of patients with babesiosis until serologic confirmation has been made.

The author is the recipient of a research fellowship for physicians from the Howard Hughes Medical Institute, Chevy Chase, Md.

ELEFTHERIOS MYLONAKIS, M.D.,
is a clinical and research fellow in infectious diseases at Massachusetts General Hospital, Harvard Medical School, Boston, and the recipient of a research fellowship for physicians from the Howard Hughes Medical Institute, Chevy Chase, Md. Dr. Mylonakis earned a doctorate degree in infectious diseases and internal medicine at the National University of Athens Faculty of Medicine and School of Health Sciences. He also completed a residency and chief medical residency in internal medicine at Miriam Hospital, Brown University School of Medicine, Providence, RI.

BACKGROUND: Current estimates of 70 cases of transfusion-transmitted Babesiamicroti, with 12 associated deaths, suggest that Babesia is a growing bloodsafety concern. The extent of Babesia infections among blood donors has not beenwell defined. To determine how common exposure to B. microti is among blooddonors, a seroprevalence study was undertaken in the American Red CrossNortheast Division. STUDY DESIGN AND METHODS: Blood donations at selected blooddrives in Connecticut and Massachusetts (2000 through 2007) were tested for thepresence of immunoglobulin (Ig)G antibodies to B. microti usingimmunofluorescence assay. Geographic and temporal trends of B. microtiseroprevalence were estimated for donor's zip code of residence. RESULTS:Overall, a 1.1% seroprevalence was identified in Connecticut, with the highestlevels found in two Southeastern counties (Middlesex and New London). Observedseroprevalence for offshore islands of Massachusetts was 1.4%. Seropositivedonations were identified from donors residing in all eight counties inConnecticut and three counties in Massachusetts. Although a seasonal peak wasfound between July and September, seropositive donations were identified inevery month of the year. CONCLUSIONS: Foci of statistically higher B. microtiseroprevalence among blood donors were observed; however, B. microti transfusiontransmission risk exists for blood collected throughout Connecticut and portionsof Massachusetts. Similarly, a seasonal peak was identified; nevertheless,seropositive donations were found year-round. Thus, geographic and/or seasonalexclusion methods are insufficient to fully safeguard the blood supply fromBabesia transmission. Steps should be taken to reduce risk oftransfusion-transmitted B. microti, perhaps through implementation ofyear-round, regional testing. http://eutils.ncbi.nlm.nih.gov/entrez/e ... rlinksPMID: 19821951 [PubMed - as supplied by publisher]

The percentage of black-legged ticks in the area infected with at least two disease-causing microbes -- the bacteria that cause Lyme disease and the parasite that causes babesiosis -- may be much higher than previously thought.

A new study, performed by Dr. Eva Sapi of the University of New Haven, collected ticks in four towns in northern Fairfield County -- Bethel, Newtown, Redding, and Ridgefield.

It found that in 2009, about 90 percent of the ticks tested had the Lyme disease bacteria. The same study showed about 30 percent of ticks tested had babesia, the parasite that causes the malaria-like illness babesiosis.

"To be honest, it doesn't surprise me at all,'' said Maggie Shaw, of the Newtown Tick-borne Disease Committee, Friday. "I've had babesiosis," she said. "My daughter has had babesiosis.''

Dr. Gary Schleiter, chief of infectious diseases at Danbury Hospital, said that the hospital has also seen an increase in cases of people with babesiosis recently.

"It's been around here for years but in the past two or three years, it seems to be increasing,'' he said. "This study confirms what we've been seeing.''

The study, done in coordination with the Fairfield County Municipal Deer Management Alliance, is in the second year of a three-year project.

For the data, Sapi collected nearly 900 black-legged ticks -- also known as deer ticks -- in the four towns in the study in 2008 and 2009.

They showed high rates of infection in all the ticks collected -- as high as 98 percent infection for Lyme bacteria and 36 percent for babesia in the 41 ticks collected near the Head O' Meadows School in Newtown.

These rates are much higher than those done by other researchers studying Lyme disease in the area.

For example, Kirby Stafford of the Connecticut Agricultural Experiment Station in New Haven has tested the blood of engorged ticks sent to the station and found much lower rates of Lyme infection in the state -- as low as 13.6 percent in Newtown and 23 percent statewide in 2008.

Stafford was unavailable for comment Friday.

At the same time, the number of Lyme disease cases in the state is rising, according to the state Department of Public Health. The state reported 3,896 confirmed cases of Lyme disease reported in Connecticut in 2008, compared to 3,058 in 2007.

By most accounts, that number under-counts the actual number of Lyme cases by a factor of 10.

Shaw and Karen Gaudian of the Ridgefield Lyme Disease Task Force said the high numbers for both diseases show the difficulties most patients face if they become co-infected with both Lyme -- caused by the Borrelia burgdorferi bacteria -- and babesiosis -- caused by the Babesia microti parasite.

Divisions of 1Infectious Diseases and 2Hematology/Oncology, Departments of Medicine and 3Pathology, New York Medical College, Valhalla; 4Division of Infectious Diseases, Rockville General Hospital, Rockville, and 5Division of Infectious Diseases, 6Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, Connecticut

Background.Babesiosis is an emerging tickborne malaria‐like infection principally caused by Babesia microti. This infection typically resolves either spontaneously or after administration of a 7?10‐day course of azithromycin plus atovaquone or clindamycin plus quinine. Although certain highly immunocompromised patients may respond suboptimally to these drug regimens, unlike the situation with malaria there has been no reported evidence that the cause of treatment failure is infection with drug‐resistant strains of B. microti.

Methods.Emergence of drug resistance in B. microti was defined as the development of a microbiologic relapse (recurrent parasitemia or a marked increase in parasitemia) in association with both clinical and laboratory abnormalities indicative of active babesiosis in a patient after 28 days of uninterrupted antibabesia drug therapy and while still receiving treatment.

Results.The clinical case histories of 3 highly immunocompromised patients who received a subcurative course of azithromycin‐atovaquone associated with the eventual development of resistance to this drug regimen are described. One of the 3 patients died of complications related to babesiosis.

Conclusions.B. microti may become resistant to azithromycin‐atovaquone during the treatment of babesiosis with this combined drug regimen in highly immunocompromised patients. Although research is needed to determine the optimal therapy for highly immunocompromised patients with babesiosis, reducing the level of immunosuppression when possible would appear to be a desirable strategy.

Received 28 May 2009; accepted 31 August 2009; electronically published 4 January 2010.

LIKE THE PREVIOUS FREE BABESIA 2009 UPDATE THIS POST AND LINK
CANNOT BE EDITED. THE WORDS OUTSIDE THE LINKS HAVE REASONS.

Some physicians, patients and laboratories are using microscopy to find
Babesia. The problem with this approach includes that there is no
benchmarkbook on the vast forms of Babesia found inside and outside blood
cells. No Babesia Hematology book exists for physicians, microscope enthusiasts
or aggressive patients interested in basic staining and blood examination.

1) While the CDC and various state departments of health (DOH)
provided a large number of core images for this book, their useful slides
show massively infected Red Blood Cells. While they are useful to show
profoundly infected people , such images in hematology are rare. Indeed,
some microscopy lovers report many markedly infected patients are ?negative?
on manual smears 100% of the time by most labs. In reality, sometimes one
needs to look 2-3 hours to see a single Babesia form. The CDC suggests
looking for 2-3 minutes for these types of protozoa infections. Massive
infections can possibly kill, cause clear RBC destruction, create massive
sickness and immense fevers, and this can lead to the discovery of new
species or sub-species. However, using catastrophic cases or any one lab
test to diagnose Babesia found in at least 30% of deer ticks is a concern.
Further, it is rare for patients to receive aggressive direct types of
testing from multiple laborat!
ories. In addition, some health workers are starting to believe indirect
testing is actually more sensitive.

2) Some images in the book use Babesia images from Fry Labs before
April/2007. PLEASE NOTE : We have not had a positive Babesia from Fry since
March/2007. Dr. Fry and I have different views at times, but are good
friends, and we feel the reason for negative Babesia slides is clear. For
various reasons Fry Labs VERY strongly avoids possible Babesia artifacts. No
one in the world can be 100% sure that some presentation of ?Babesia? is not
an artifact. My position is to accept any very highly suspicious image. Yet
his position is to avoid any false positives. Honorable people have
different priorities and goals. Fry laboratory is also spending massive time
and income to become involved in DNA lab innovation as their priority. Other
reasons for this direction are proprietary. In conclusion, the use of the
Fry smear for Babesia alone seems unwise.

3) I wrote this book some years ago. Any TBD book is likely slightly
outdated in months , although some things are true for thirty years. This
is common for anyone reading and passionate about credible new ideas. I have
no time to offer an updated edition. O utdated comments and errors may
exist. We have radically changed much of what we do even in the last six
months.

YOU MAY POST THIS FREE ON ANY SITE WITH THE WORDS LISTED IN THIS
EMAIL WITH NO DELETIONS .

It?s an apparent medical dilemma - a disease whose victims may suffer vague symptoms for weeks or months as physicians ponder the cause, sometimes coming to the right diagnosis just hours too late to save the patient.

The affliction is babesiosis, yet another disease passed on to humans by a deer tick and recognized for decades without attaining the notoriety of two other life-threatening diseases carried by the same tick, Lyme and anaplasmosis (also known as ehrlichiosis.)

If you haven?t heard of babesiosis, you have lots of company. The majority of those who were asked by this reporter if they were familiar with the disease indicated they had never heard of it. A few others said they knew someone who had had it but little else.

However, those interviewed who had had close contact with the disease were surprisingly eager to talk about their experiences, some of which were harrowing tales. That included two people whose close relatives had suffered and died just hours after a diagnosis of babesiosis was reached in a hospital emergency room, too late to save them.

Several others counted themselves among the ?lucky? because either they were examined by a doctor who admitted to not know the cause of the symptoms which often resemble those of the flu, and referred them to someone who did. Or they were examined at a facility that sometimes orders simultaneous tests for three of the known tick-borne diseases. That procedure may have saved lives this past summer when at least four cases of babesiosis were diagnosed promptly on the Lower Cape.

For background to the uninitiated, babesiosis is a disease of the red blood cells where parasites, similar to cases of malaria, attempt to destroy those cells. Victims most at risk when they contract babesiosis are the elderly and those at any age with chronic diseases or physical impairments that could compromise recovery. Also at risk are those who ignore chronic symptoms when the first or second physician they consult fails to diagnose their condition. Fortunately, the spleen, one of whose duties is to filter red blood cells, can assist in recovery despite a failed diagnosis, especially in younger victims who do not have compromising health conditions.

A 77-year-old who had retired to Brewster and had no potentially compromising physical issues sought out a heart specialist when he was having breathing problems, weakness and loss of weight, three of the many possible symptoms for babesiosis. He passed a set of tests for heart disease and was told he had no problems in that area. When the symptoms continued, he consulted his regular physician who thought he might have pneumonia. Once again no health problems were identified. These efforts to understand what was wrong continued over a period of five or six weeks, his wife said. Neither doctor had ordered a blood test.

His condition continued to deteriorate until finally his wife took him to the emergency room at Cape Cod Hospital. The doctor ordered a blood test and it showed he had an unusually high count of white blood cells caused by babesia parasites. The diagnosis, even after he was given multiple transfusions, was too late and he passed away.

Another sad example is a relatively young person from Orleans who died from babesiosis. He was 53 and suffering from Crohn?s Disease when he was bitten by an infected tick. His mother said he misconstrued his symptoms as an attack of Crohn?s so he did not call a physician. When his mother checked on him she became very concerned and had him transported to a hospital. A blood test confirmed he had babesiosis, but the parasites had done their job well and he died hours later.

Survivors Tell Their Stories

Happily, other Cape Cod residents diagnosed with babesiosis have more encouraging tales to tell. Several victims of the disease in the Wellfleet/Provincetown area last summer were diagnosed promptly because their physicians ordered the composite test for tick-borne diseases and babesiosis was identified. All have expressed concern and impatience at their slow but steady recovery after taking medication developed to replace quinine (which at one time was the only known treatment but could have harmful side effects.) One victim, who was diagnosed with Lyme at the same time as babesiosis, continues to have persistent breathing problems and other symptoms which she attributes to tick-related disease and is seeking other types of treatment.

For another Wellfleet victim, diagnosis was elusive. She said in the summer of 2008 she had been feeling vaguely ill for months, which can be typical of babesiosis, whose symptoms may be so mild it is not recognized. When her situation finally became acute she was sent by ambulance to Beth Israel Hospital in Boston, where babesiosis was diagnosed. She spent at least eight days in the hospital while transfusions were administered to counteract anemia caused by the red blood cell parasites. She could be termed one of the ?lucky? ones as she is in her 80s and recovery is expected to be more difficult, or, at worst, questionable, for the elderly.

Babesiosis for an Orleans resident came on slyly, catching her unawares as she drove to the Hyannis office of the non-profit organization where she volunteers. Dozing off as she drove on Route 6, she was awakened by driving over the rough edge of the highway surface just as she was about to run off the road.

Thinking only that it was a case of overtiredness from not feeling well recently, she continued on to the office, where a fellow volunteer, startled by her appearance, asked her what was the matter. She found she had a temperature of 104 degrees. A visit to her doctor?s office resulted in being given a prescription for an antibiotic and the admonition to go to the emergency room at Cape Cod Hospital the next morning if she did not feel better.

She took his advice. A blood test revealed she had babesiosis. She received at least three transfusions over a week?s time.

?They gave me another one just as I was dismissed,? she said, with the advice it might take at least six months for her blood to regain its balance and she would start feeling ?normal.? She said the timing was right on.

But a South Chatham woman who was in her 50s when she contracted babesiosis said it took her over 10 months to fully recover. Her symptoms had included fever and an incredible headache, enough for her physician to insist that she go to the hospital for blood tests, fearing meningitis. The diagnosis was babesiosis.

The frustration of victims of tick-borne diseases - from a creature that is so small in the ?nymph? stage it can hardly be seen, and sometimes can be scratched off without any awareness that the victim has been bitten ? is paramount, as those interviewed were eager to impart. They are dismayed they have had to make real life changes to avoid exposure to ticks. For instance, gardening and casual walks in the woods and dunes which have been so important to their lives must now be done with concern for their health, and conscious steps for self protection.

A Growing Threat

In the spring, like any newborn, the nymphs are voraciously hungry, laying in wait on the tips of leaves, moist grasses (they require a moist habitat), in wood piles and bushes, for a warm-blooded animal or person to pass by close enough to transfer themselves to it, the victim unaware and seemingly powerless to protect itself.

As the nymph stage progresses in June from the size of a poppy seed to eventually the size of an immature wood tick, its characteristic reddish brown body is more identifiable, but it is still so small that it is possible to be unaware of its presence, usually in the more protected and moist parts of the body -- behind the knees, ears, base of neck and the like.

Two other deer tick-borne diseases are more familiar to the general public than babesiosis - anaplasmosis, which involves parasites of the white blood cells (also known as ehrlichiosis), and Lyme disease, named after the town in Connecticut where it was first recognized in the 1970s. The strange symptoms of Lyme which many doctors early on were finding difficult to pinpoint, raised the concern of parents and friends as they saw their loved ones and associates in pain and signs of progressive loss of health. Their concerns slowly triggered the long process of raising consciousness about tick-related diseases and their troubling, potentially long lasting and threatening elements.

The deer tick is not alone in its transgressions against humans. The wood tick (larger than the deer tick but with white graphitic-like marks on its back) carries yet another serious disease, Rocky Mountain Spotted Fever, also life threatening if not recognized and treated promptly. Ironically, one could hardly call the wood tick preferable to a deer tick, but at least because of its size - about twice that of a deer tick - it can usually be felt crawling on your skin and removed before it imbeds itself. (An imbedded tick will not transfer its diseases if it is removed up to 24 hours after it became imbedded, according to some reports.)

The Cape Cod Cooperative Extension in Barnstable has taken a stand against ticks on Cape Cod and the Islands and is attempting to rid the area of them, using knowledge of the deer tick?s life cycle - from deer to field mice to humans. If the cycle can be broken the threat will be lessened. The question is how to find the funds to accomplish such a task.

One such attempt that was state funded included setting up feeders for deer in the woods where a deer is lured to a feeder placed so that it rubs against four posts on which pesticides had been deposited. If successful, the pesticides kill the ticks. But the failing economy caused the funds for the program to be cut. David Simser of the Extension Service said he has no idea when and if such programs will be refunded, although he hopes some will be coming forth from the Environmental Protection Agency.

?I?ve got my fingers crossed,? Simser said.

So protection from ticks, at least for the time being, apparently mostly falls to the residents of the area to assist by appropriate management of their properties, as well as more intensive education of the public by local organizations.

County Leads Education, Prevention Campaign

The Cape and Islands Tick Disease Task Force, founded over 10 years ago by Truro biologist Brenda Boleyn, provides information and seminars to keep doctors and other professionals updated on tick issues, as well as initiatives in alerting the public.

The extension service has put out a booklet, which is available by contacting it at www.capecodextension.org. It contains advice for reducing the number of deer ticks, for instance, by clearing property borders of low lying limbs, leaves and grass. It lists the safe uses of pesticides and tips for disposal of clothing when working outside or walking in the country. There are suggestions for plantings and other ways to make gardens less attractive to deer, mice and other animals that might carry babesia parasites.

The extension service in 2007 compiled data from a survey of deer ticks on the Cape (Sandwich to Yarmouth as well as the Islands) and the diseases they carry. In that report, an average of 47 percent of the ticks tested carried Lyme disease. More alarming, an average of 5 percent of the ticks in three of the towns where testing took place - Harwich, Yarmouth and on Martha?s Vineyard - carried all three of the diseases, Lyme, babesiosis and anaplasmosis. Funding for testing of the Lower Cape has not been secured.

Simser said more recent figures indicate there were 25 confirmed cases of babesiosis in Barnstable County in 2008 and a total of 51 cases for the combined counties of Barnstable, Dukes and Nantucket, or an increase of 34 percent of cases in 2008 over those in 2007. He said the current state budget does not include tick testing.

Education, be it through the extension service or other means, includes understanding of tick habitats so they can be avoided, such as wet, swampy areas, wood piles that may contain damp rot, as well as early morning dew- laden grasses, along the shore or in woods and open fields. Also pertinent is that the deer tick, unlike the wood tick, is present year round, with the potential for transmitting diseases when temperatures are above 30 degree. Clothing can also help protect an individual. White socks drawn up over light-colored trousers will make ticks more visible. Throwing clothing into a dryer for 20 to 30 minutes could help get rid of ticks missed visually. Unfortunately, a hot shower or bath may annoy but not kill ticks so full body checks at night are critical after potential exposure, including double examination of key areas such as the hair lines and behind ears.

Joyce Johnson is a free lance reporter who has had personal experience with tick-borne disease. She was a staff reporter for The Cape Codder newspaper for 16 years where she wrote extensively about Lyme Disease on Cape Cod. She may be reached by e-mail at www.joysculpt1@comcast.net.

"I have personally conquered Babesia Duncani I want to share my experience with you. I have since used similar treatments in patients.

I began therapies using high doses of Artemesinin (Allergy Research) with Zhang herbal Artemesiae. Dr Zhang has isolated the active ingredient of Artemesinin (the active portion of Artemesia), and I do believe his Artemesiae is very effective. I used this combination with the Cowden herb, Enula for the first several months of my treatments. Many symptoms cleared but I relapsed after 6 months developing sweats, horrific headaches, and mood swings.

I was the then treated with Doxycycline, Mepron and Zithromycin. I believe that these drugs should be given the full length of the RBC- for 4-5 months, which is what I did. My symptoms (horrendous headaches and sweats) improved but I was left with persistent hepatomeglay, raised liver enzymes, occasional sweats, and mood swings.

My mood was immediately improved with Lamictal, which treats the underlying problem seen in most chronic Lyme patients, Limbic Seizures. I used low doses of Lamictal (25 mg) and gradually increased as needed to control the mood changes. I have remained on 150 mg twice daily as my treatments continue.

I am nearing the end of my intravenous treatments with Tigacillin and Levaquin. I am enjoying normal days on my drug holidays - which I do every 2 weeks. I will be doing IV Meropenem and oral Rifambutin before stopping IV and changing to oral medications, Rifambutin, Omnicef, and Minocycline (in 2 week cycles on and off).

I realize that pulsed therapies are controversial, but after several months of daily treatments, and once Babesia is under control, I find them effective and most importantly one can finally achieve a sense of control while rehabilitating from this disabling disease. The drug holidays are also important to see how well the immune system is coping and to give one a sense of improvement and respite from herxing. During drug holidays I recommend intravenous vitamins, infrared sauna, and juicing for a detox.
I now recommend that all Chronic Lyme patients be treated simultaneously for these 3 infections, no matter what tests show. The current tests for Bartonella, in particular are very insensitive. Assume that patients have these 3 infections, otherwise you will be chasing your tail constantly with therapy, and until Babesia is brought under control, the immune system will not strengthen, and patients will remain unwell.

Division of Parasitology and Parasitic Diseases, Department of Preclinical
Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences,
Warsaw, Poland. wojciechzygner@yahoo.pl

The purpose of this study was to specify the occurrence and prevalence of
Babesia microti in hard ticks removed from dogs in Warsaw (central Poland).
Among 590 collected ticks, 209 were identified as Ixodes ricinus, and 381 as
Dermacentor reticulatus. B. microti DNA was detected in 11 out of 590 (1.86%)
samples of ticks. The DNA of the parasite was detected only in lysates from
female I. ricinus ticks (11 out of 193; 5.7%). The result of this study is the
first evidence of B. microti in I. ricinus ticks in Warsaw.

Transfusion-acquired babesiosis can be an asymptomatic or self-limited febrile
hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant
course with the development of life-threatening complications may be seen in
immunocompromised or splenectomized patients. As in malaria, erythrocyte
parasitemia is often associated with nonimmune hemolysis, and can be treated
with erythrocytapheresis. Just as warm autoantibodies have been reported in
malaria infection, the development of autoantibody-mediated immune hemolysis has
been reported in babesiosis. We treated a previously healthy male with multiple
injuries from a motor vehicle accident necessitating massive transfusion. Late
in the hospitalization, his blood smear revealed Babesia microti, confirmed by
PCR study and serology. This was eventually traced to a unit of blood from an
asymptomatic blood donor that was transfused during his initial trauma care.
Specific antibiotic therapy was begun, and severe hemolysis from a high parasite
burden required red blood cell exchange which led to rapid abatement of the
hemolysis. He had a positive DAT (IgG with a pan-reactive eluate) but no serum
autoantibody. This persisted for 10 days following cessation of hemolysis, and
became negative while still on antibiotics while his parasite burden became
undetectable. Reports of autoimmunity associated with community acquired
babesiosis often have severe hemolysis from their autoantibodies, but our case
shows that autoantibodies may also follow transfusion-acquired babesiosis. The
nature of the autoantigen is unknown. J. Clin. Apheresis, 2010. (c) 2010
Wiley-Liss, Inc.

We report 2 cases of babesiosis in immunocompetent patients in France. A severe
influenza-like disease developed in both patients 2 weeks after they had been
bitten by ticks. Diagnosis was obtained from blood smears, and Babesia divergens
was identified by PCR in 1 case. Babesiosis in Europe occurs in healthy patients, not only in splenectomized patients.

We report the first molecular evidence of the presence of Babesia sp. EU1 and Babesia microti in Ixodes ricinus ticks in Belgium. A 1-year national survey collected 1005 ticks from cats and dogs. A polymerase chain reaction technique amplifying a part of the 18S rRNA gene detected Babesia spp. in 11 out of 841 selected and validated tick extracts. Subsequent sequencing identified Ba. microti (n = 3) and Babesia sp. EU1 (n = 6). This study has demonstrated a low infection rate (1.31% with 95% CI: 0.65?2.33) of Babesia spp. carriage in I. ricinus ticks in Belgium but, for the first time, reports two potentially zoonotic species belonging to this genus. Coinfection with Ba. microti and Borrelia burgdorferi sensu stricto also was demonstrated. In addition, this study clearly demonstrates that inhibitors of polymerase chain reaction amplification are present in engorged ticks.

Source
Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, USA. mason.reichard@okstate.edu.
Abstract
Babesia spp. are tick-transmitted apicomplexan hemoparasites that infect mammalian red blood cells. Our purpose was to determine the prevalence of Babesia infection in a colony of captive baboons and to evaluate potential experimental routes of the transmission of the hemoparasite.
DNA was extracted from the blood of baboons and tested for infection with Babesia by PCR and primers that amplify the 18s rRNA gene of the parasite. The overall prevalence of infection of Babesia in the baboon population was 8.8% (73 of 830). Phylogenetic analysis of the sequenced DNA from 2 baboons revealed that the Babesia isolate found in captive baboons was a novel species most closely related (97% to 99%) to B. leo.
Blood from a Babesia-infected donor baboon was inoculated intravenously, intramuscularly, or subcutaneously into 3 naive baboons. The intravenously inoculated baboon was PCR-positive at 7 d after inoculation; the 2 baboons inoculated by other routes became PCR-positive at 10 d after inoculation.
All 3 baboons remained PCR-positive for Babesia through day 31. Baboons experimentally inoculated with the new Babesia isolate did not exhibit clinical signs of babesiosis during the experiments.
We demonstrated that captive baboons are infected with a novel Babesia isolate. In addition we showed that Babesia can be transmitted in the absence of the organism's definitive host (ticks) by transfer of infected blood through intravenous, intramuscular, and subcutaneous routes to naive baboons.

CHICAGO ? A tick-borne infection known as Babesiosis, which can cause severe disease and even death, is becoming a growing threat to the U.S. blood supply, government researchers said Monday.
There are currently no diagnostic tests approved by the U.S. Food and Drug Administration that can detect the infection before people donate blood.
A 31-year study by the U.S. Centers for Disease Control and Prevention now suggests the parasitic infection may be increasing.There are currently no diagnostic tests approved by the U.S. Food and Drug Administration that can detect the infection before people donate blood.
Babesia infections are marked by anemia, fever, chills and fatigue, but they can also cause organ failure and death.
The still rare disease is known to occur in seven U.S. states in the Northeast and Upper Midwest in the spring and summer.
But a study led by Dr. Barbara Herwaldt of the CDC, published in the Annals of Internal Medicine, found cases had occurred year-round and in states where Babesia parasites are not found -- including as far away as Texas and Florida.
States in which the parasite occurs naturally are Massachusetts, New York, Connecticut, Minnesota, Rhode Island, New Jersey and Wisconsin.
Of the 162 cases of Babesia infection caused by blood transfusions between 1979 and 2009, nearly 80 percent occurred between 2000 and 2009.
"Babesia microti has become the most frequently reported transfusion-transmitted parasite in the United States," CDC researchers wrote, far outpacing malaria infections, which accounted for 49 cases of transfusion-associated disease during the same period, including just five cases during 2000-2009.
Premature infants appear to be especially vulnerable.
A separate study published Monday in the journal Pediatrics by a team at the University of Nebraska looked at seven cases of transfusion-associated Babesiosis in premature infants.
They found blood transfusions from two infected units of blood caused all seven of the cases of Babesiosis.
Symptoms of the infections varied widely, but babies with the lowest weights at birth were at greatest risk of serious infection.
The authors warned doctors in areas in which Babesiosis occurs to be watchful for cases in premature infants exposed to blood transfusions.
The CDC researchers called for better ways to prevent and detect cases of transfusion-associated Babesiosis.

"Our findings underscore the year-round vulnerability of the U.S. blood supply -- especially, but not only -- in and near Babesiosis-endemic areas.
"They also highlight the importance of multi-agency collaborative efforts to detect, investigate, and document transfusion cases; to assess the risks for transfusion transmission; and, thereby, to inform the scope of prevention measures."
To deter transfusion-linked Babesiosis, the CDC in January said public health departments should report all cases of the infections to the CDC.

Dutchess at center of rising tick threat - More ticks, people infected with babesiosis

John Darcy, 68, of Beacon, has suffered with the tick-borne illness, babesiosis, for more than five years. Darcy, who takes 8,000 milligrams of amoxicillin each day, is feeling better now and has regained the strength needed to pull back his compound bow for deer and turkey hunting. / Spencer

Babesiosis and the Blood Supply: LYME DISEASE -- Babesiosis and the Blood Supply. Video by Chrissie WilliamsABOUT THIS SERIES

This is part 8 in a Poughkeepsie Journal series on the prevalence and problems of Lyme disease and other tick-borne illnesses. Go to www.poughkeepsiejournal.com/lyme to read previous installments on treatment and testing and to view videos on Lyme disease and babesiosis.Related Links

When John Darcy began to get sick some eight years ago, it was in slow, painful increments. An outdoorsman and athlete for years, the Beacon resident, now 68, found he could not jog or bike as far. Aging, he thought. He suffered soreness he had never known. Push through it, he told himself.

But soon he was losing his balance. He lacked the strength even to pull back his bow. He could not dress himself or lift his arm to shave.

As he lost weight and vitality, Darcy was prodded and tested for everything, it seems, but the thing it turned out to be: a burgeoning disease called babesiosis.

“It was never even mentioned,” said Darcy, 68, a retired Beacon IBMer and correction officer, who was also diagnosed with Lyme disease in a one-two tick-borne punch. “I never even heard of the word.”

That may change. Someday, perhaps not so far into the future, the so-called “emerging” malady known as babesiosis may join Lyme disease as another environmental scourge wrought by the tiny and insidious black-legged tick. And Dutchess County is at the crest of this gathering wave.Dutchess ranks first

In 2011, Dutchess ranked first in New York state and 13th nationally in per-capita rate of the disease, according to statistics released exclusively to the Poughkeepsie Journal by the U.S. Centers for Disease Control and Prevention. The county had the nation’s third-highest number of cases, which rose from 4 in 2002 to 53 in 2011.

“The Hudson River Valley has eclipsed Long Island for Lyme disease and babesiosis,” said Dr. Alan MacDonald, a long-time Lyme researcher and Long Island pathologist. “You’re up to your neck in ticks that carry babesiosis.”

Babesiosis is a disease, like malaria, most often linked to a protozoan parasite called Babesia microti, though other strains cause illness too. It is usually treated with antibiotics and anti-malarial drugs.

Just why the disease is emerging now – long after Lyme disease hit– may have something to do with what scientists call “reservoirs” of infection: birds and mammals that infect the ticks that in turn bite people.

1 Yale School of Public Health and Yale School of Medicine, New Haven, CT, USA 2 Overlook Medical Center, Summit, NJ and Mount Sinai School of Medicine, New York, NY, USA

AbstractBabesiosis is a worldwide emerging infectious disease caused by intraerythrocytic protozoa that are transmitted by Ixodid ticks, or less commonly through blood transfusion or transplacentally. Although headache and lethargy are common symptoms, babesiosis is uncommonly associated with specific neurological dysfunction in humans. Decreased level of consciousness or coma are rare complications that are associated with severe and often fatal disease but the pathogenesis is unclear.

Babesiosis is an emerging zoonosis caused by protozoan parasites of the genus Babesia. The disease is endemic primarily in the Northeast and upper Midwestern United States. The genus Babesia comprises multiple species of apicomplexan parasites that infect red cells of many vertebrate hosts. Babesia divide and replicate in the hosts' red blood cells and are called piroplasms due to their pear-shaped appearance within the RBCs (Figure 1). They are transmitted by ixodid tick vectors as they feed on a blood meal from the host [1]. Babesiosis has long been recognized as an economically important disease of cattle, but only in the last 40 years has Babesia been recognized as an important pathogen in man.thumbnailDownload:

Figure 1. Different forms of Babesia divergens in human RBCs as seen on a Giemsa-stained smear from in vitro cultured parasites (ring, dividing figure eights, Maltese cross parasites, and multiply infected RBCs).doi:10.1371/journal.ppat.1003387.g001

The majority of cases in the United States are caused by B. microti and occur in the Northeast and upper Midwest [2]. A small number of infections caused by B. duncani and B. duncani–like organisms have been reported on the West Coast from California to Washington State [3]. Additionally, B. divergens–like organisms have been reported in Kentucky, Missouri, and Washington State [4]. In Europe, almost all reported cases have been due to B. divergens, and a few have been caused by the EU1 species, now called B. venatorum [5], [6]. Sporadic cases of babesiosis have also been reported in Asia, Africa, Australia, and South America [7].

The symptomatic spectrum of human babesiosis is broad, ranging from clinically silent infections to intense malaria-like episodes resulting occasionally in death. When present, symptoms typically are nonspecific (fever, headache, and myalgia) [8]. Human babesiosis is a zoonosis, and the natural acquisition of human disease is the result of interactions with established zoonotic cycles. Emerging diseases are defined as “novel, re-emerging, or drug-resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future.” Because of the increasing number of human infections since 1990, human babesiosis can be considered an emerging disease [7]. A number of factors have contributed to the “emergence” of human babesiosis, including a heightened awareness among physicians, a changing ecology, and a larger population of immunocompromised individuals, where fatalities have occurred. This led the Centers for Disease Control and Prevention to add babesiosis to the list of nationally notifiable diseases in 2011.Why Has Babesiosis Become a Major Transfusion Threat?

In the United States, almost 5 million recipients undergo blood transfusions annually. These transfusion recipients are at potential risk of exposure to transmissible pathogens like Babesia from donor blood [9]. This is because, besides their natural route of transmission, the parasite is also transmitted by transfusion of blood products, as its red cell location provides an appropriate niche to facilitate its transmission. In fact, as the frequency of clinical cases has risen, there has been an associated increase in transfusion-transmitted Babesia (TTB) [10], making babesiosis the most frequent transfusion-transmitted infection with approximately 162 cases reported since 1980 and 12 associated fatalities in the period 2005–2008 [9], [10]. The major reason for this increase is that babesiosis can be asymptomatic, indeed clinically silent, in healthy adults who are the dominant blood donors. In one study, asymptomatic individuals who tested negative for Babesia in Giemsa smears had detectable amounts of B. microti DNA in their blood for three months [11]. Blood transfusion recipients generally present with more severe illness, as they have at least one of the risk factors for severe babesiosis, including extremes in age, lack of a spleen, hemoglobinopathies, cancers, HIV, and use of immunosuppressive therapy [9]. In these patients, babesiosis may be refractory to standard antimicrobial therapy [12] and may result in prolonged illness or death. Historically, babesiosis has been treated with a weekly course of clindamycin and quinine [13]. However, this combination of drugs can be so debilitating in some patients that it prevents successful completion of therapy. Physicians now recommend the equally effective combination of azithromycin and atovaquone [14]. Unfortunately, recent reports indicate that B. microti may become resistant to azithromycin-atovaquone in highly immunocompromised patients [12]. This drug resistance needs to be investigated further in the public health context. Among the 18 cases of TTB identified by the hemovigilance program at the American Red Cross between 2005 and 2007, ~30% had a fatal outcome [15]. Some studies suggest a transmission risk as high as 1 per 601 blood units in areas of the highest prevalence [16]. To complicate this situation further, B. microti is known to survive and remain viable under blood storage conditions (4°C) for up to 35 days in RBCs and indefinitely in cryopreserved RBCs [17].What Is the Status of Current Blood-Banking Safeguards against Babesiosis?

The current strategy of blood screening, nationwide, to prevent transfusion-transmitted babesiosis (TTB) relies on a donor questionnaire to identify potential deferrals [10]. Donors who answer in the affirmative to a query of having a history of babesiosis are barred from donating from that day forward. This reliance on donor response to risk factor questions has many shortcomings as can be seen by the substantial increase in TTB in the last ten years. While it permanently excludes prospective blood donors with a history of babesiosis, it appears to be of limited value, presumably because infected blood donors experience asymptomatic infection or remain infectious long after symptoms have resolved. This current policy also impacts the blood supply because infectivity may be finite and patients who have had symptomatic babesiosis in the past might no longer be infectious. Systematic laboratory screening of the blood supply in the form of state-of-the-art FDA-licensed serological and nucleic acid testing (NAT) assays is available for many blood-borne pathogens like HIV and hepatitis to prevent their spread by transfusion. Unfortunately, the lack of comparable, sensitive screens available for vector-transmitted protozoal parasites like Babesia has resulted in the current complete dependence on a donor response questionnaire to safeguard the nation's blood supply.What Tests Are Currently Available to Detect Babesia?

The major barrier to preventing parasite transmission is the absence of a licensed assay to detect the parasite in blood donors. At the diagnostic level, there are both antibody and DNA detection tests available that are not suitable for blood donor screening for a number of reasons. The qPCR detection assays for B. microti exploit the gene encoding 18s rRNA as the template [18], [19] and have the advantage of detecting the parasite, if present, through the entire course of infection. As a diagnostic it is an efficient screen, as it is used to detect symptomatic infection where both parasite levels and volume of blood available for testing are high. Screening of donor blood for infectious organisms typically relies on a few milliliter sample of blood taken for analysis. As the parasite is present at a very low parasitemia in donor blood, this small sample of blood may not harbor sufficient parasites to yield a detectable amplification signal. This sampling limitation is currently the major impediment to deploying qPCR assays in donor blood testing. The antibody detection assay currently in use as a diagnostic is an immunofluorescence assay (IFA) screening for antibodies in sera of blood donors to smears of fixed parasites grown in hamster or mouse RBCs [18], [19]. Although rigorous data on the kinetics of the immune response to the parasite is not available, the window period in early infection, where antibodies are not present in circulation, may result in missed detection. Similarly, after the infection is resolved, antibodies may persist, resulting in erroneous positives that will exclude donors from giving blood. A high-throughput platform to enable use of IFA technology would also have to be developed to facilitate its use as a mass donor screen. Even when IFA and qPCR tests are combined, limitations persist, presenting an urgent need for a more sensitive and specific blood screening assay that can be used at blood centers for Babesia detection.Would Pathogen Reduction and/or Inactivation Technology Work for Babesia?

Pathogen reduction and inactivation technologies represent a different approach from testing donors for recognized pathogens. If sufficiently broad-spectrum and robust, they may prevent transmission of many emerging blood-borne infectious agents in the future, if they do not harm the recipient or blood component. Multiple pathogen inactivation (PI) technologies for the treatment of platelet or plasma components have been developed and are in routine use, based on methylene blue, psoralen, and riboflavin technologies. As Babesia is an intra-erythrocytic parasite, PI technologies would have to target the red cell component of the blood. No pathogen reduction technology for RBC units is commercially available at the present time, although there are two major platforms that are poised to change this status. The first is a technology (Cerus Corporation, Concord, California) based on the use of S-303, an intercalator group that inserts into the helical region of the nucleic acid, an effector group that allows covalent modification of nucleic acid, and a central frangible bond that allows degradation of the compound [20]. The second is the Mirasol PRT system (TerumoBCT Biotechnologies, Lakewood, Colorado), which uses a riboflavin additive that is UV light-activated to treat platelets, plasma, and whole blood [21]. Both processes have been shown to be effective against a variety of blood-borne pathogens, including Babesia species [22] (Cursino-Santos et al., unpublished data).

In summary, TTB has become one of the most commonly reported transfusion-transmitted infections in the United States. Thus, there is an urgent need to develop sensitive and specific methods for screening for this pathogen or alternative methods for eliminating it from the blood supply. Uncovering the basic biology of the parasite, including the identification of immuno-dominant antigens that could be used in designing more sensitive screens, may represent the path forward.References

UPDATE 2011- Babesia duncani (aka WA1) is normally described in patients on the west coast (USA). Doctors have also been testing east coast patients and finding they are infected with the B. duncani strain, often in addition to being infected with the Babesia microti strain. The Babesia duncani strain can not be detected on the standard Babesia microti tests. Your doctor should order both the Babesia duncani test along with the Babesia microti test if Babesiosis is suspected.

General Information: Many Lyme disease patients have one or more tick borne co-infections. In addition to the Lyme infection, patients can also be infected with tick-borne mycoplasma, a rickettsia and/or a protozoa. One study indicates over 1/2 of the Babesiosis patients also have Lyme disease.

Testing: Many doctors familiar with babesiosis will diagnose and treat based on history and symptoms due to the failure of many tests to detect the infection, especially the longer the person has been infected. Antibody tests from Quest Lab (multiple strains) and PCR tests for babesiosis can be useful if positive, but a negative result does not rule out the disease. The organism is rarely seen in blood smears. Testing can be done at IGeneX Lab or other labs.

Treatment: A combination of Atovaquone (Mepron) and Zithromax or Baixin is currently being used to treat Babesiosis.** This combination is reported to have less potential side effects than quinine and clindamyacin.

Re-treatment or long term treatment is often needed in chronic and long-standing cases. Patients may experience a worsening of the condition and symptoms while treating Babesiosis (reported in some to be on the 3-4 day, and then again at the 3-4 week mark). Once this occurs, they will enter into a recovery phase.